An investigation is planned of the sources and mechanisms of calcium mobilization in excitation-contraction coupling in smooth muscle, both vascular and nonvascular. A series of 4-aryl-1,4-dihydropyridines (derived from BAY-1040 (Nifedepine) that appear to function as potent Ca2 ion channel antagonists will be analyzed to correlate their inhibitory activity with substituent character, solid state structure (x-ray) and electronic indices. This work will use g. -p. ileal smooth muscle, where Ca2 ion channels are established as playing an important role in E-C coupling, and this same preparation will be used with a 3H or 131I-labelled derivative to attempt to determine the binding characteristics of one of these agents, to provide an estimate of Ca2 ion channel density and to serve as a preliminary approach to the eventual isolation of Ca 2 ion channel components. In the same g.p. ileal preparation it is intended to correlate 45Ca influx (measured by the "lanthanum method") with the relative abilities of a series of muscarinic agonists to initiate mechanical response. In vascular smooth muscle from normotensive and hypertensive rats (spontaneous, DOCA) an attempt will be made to correlate changes in total Ca2 ion, intracellular Ca2 ion, 45Ca exchange and the action of Ca2 ion antagonists with the differences in reactivity established in the hypertensive tissue. This work will use aorta, portal vein and carotid and iliac arteries.